Expression Patterns of Serotonin Receptors 1А and 7 in the Brain of Rats with Genetically Determined Fear-Induced Aggressive Behavior or the Lack of Aggression

Abstract—Serotonin receptors of subtype 1А (5-HT1A) are involved in the regulation of aggressive behavior. New data show that 5-HT1A receptors are capable of heterodimerization and antagonistic interaction with type 7 serotonin receptors (5-HT7); hence, it is important to study the involvement of 5-НТ7 receptors in aggressive behavior. Specifically, it is necessary to study the patterns of co-expression of 5-НТ1А and 5-НТ7 receptors in the brains of animals that differ in the degree of genetically defined aggression. In this paper, we have studied the expression of serotonin 5-НТ1А and 5-НТ7 receptors in several cerebral structures of rats with genetically defined aggressive behavior or the lack of aggression. We have revealed significant changes in the expression of these receptors both at mRNA and receptor protein levels. Of particular interest is the changes in the levels of the membrane protein of 5-НТ1А and 5-НТ7 receptors in the midbrain and hippocampus of aggressive rats. A decrease in the level of 5-НТ1А receptors in the midbrain is associated with an increase in the level of this receptor in the hippocampus; meanwhile, the level of 5-НТ7 receptor is increased in the midbrain and decreased in the hippocampus of aggressive rats compared to tame animals. These data indicate interaction between 5-НТ7 and 5-НТ1А receptors. In addition, the expression of 5‑НТ7 receptors is increased in the frontal cortex and the mRNA level of the 5-НТ7 receptor gene is decreased in the hypothalamus of aggressive rats compared to tame animals. Therefore, significant changes in the expression of 5-НТ7 receptors in the brain of rats selected for a high level of fear-induced aggression towards humans have been revealed for the first time. Genotype-dependent peculiarities of combined expression of 5-НТ1А and 5-НТ7 receptors have been revealed in the investigated brain structures. Our data suggest that interaction between 5-НТ1А- and 5-НТ7-receptors may be an important factor in the regulation of genetically defined aggression.

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Funding

Animal housing was supported by budget project No. 0324-2019-0041-C-01. This study was supported by the Russian Science Foundation (grant No. 19-15-00025).

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Correspondence to A. S. Tsybko.

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Conflict of interest. The authors declare that they have no conflict of interest.

Ethical approval. The experimental animals were treated and all procedures were performed in accordance with the international rules for the treatment of animals stated by the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80023), 1996.

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Abbreviations: 5-HT, serotonin; 5-HT1A, serotonin 1A receptor; 5-HT7, serotonin 7 receptor; rPol_II, DNA-dependent RNA polymerase II; GAPDH, glyceraldehyde-3-phospahte dehydrogenase; RT, reverse transcription; PCR, polymerase chain reaction.

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Ilchibaeva, T.V., Tsybko, A.S., Kondaurova, E.M. et al. Expression Patterns of Serotonin Receptors 1А and 7 in the Brain of Rats with Genetically Determined Fear-Induced Aggressive Behavior or the Lack of Aggression. Neurochem. J. 14, 180–186 (2020). https://doi.org/10.1134/S1819712420020051

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Keywords:

  • highly aggressive and tame rats
  • quantitative RT-PCR
  • Western-blot
  • serotonin
  • 5‑НТ1А-receptor
  • 5-НТ7-receptor